DESCRIPTION (the applicant's description verbatim): Re-endothelialization (rET) at sites of spontaneous or iatrogenic disruption has classically been considered to result from the migration and proliferation of endothelial cells (ECs) from endothelium adjacent to the site of injury, including endothelium lining the branch vessels which originate within the injured vascular segment. Preliminary data from our laboratory and others', however, suggests that neighboring ECs may not constitute the exclusive basis for endothelial repair. These studies suggest that circulating cells derived from the bone marrow (BM) and exhibiting phenotypic features of ECs are capable of homing to sites of arterial injury and incorporating into neoendothelium. Accordingly, the goal of the studies outlined in this proposal is to delineate the contribution of BM-derived endothelial progenitor cells (EPCs) to the maintenance and repair of vascular endothelium. The proposed experiments have been designed to test specific hypotheses, organized according to three Specific Aims. The first Specific Aim is to establish definitive evidence regarding the BM origin of EPCs which incorporate into neoendothelium. These experiments will be performed in murine and rodent models of arterial injury following transplantation of BM from Tie2/LacZ transgenic mice to immunodeficient animals. Specific Aim 2 is designed to investigate the impact of systemic pathology on EPC kinetics and incorporation. Specific Aim 3 is organized to explore the impact of EC mitogens, EC antagonists, and genetic engineering on EPC incorporation into neoendothelium.